The spin-1/2 nuclei of 3He and 129Xe can be hyperpolarized to 10^5 times their thermal equilibrium value, by spin- exchange collisions with Rb atoms that have been "optically pumped" by circularly polarized light entirely into one electron spin state. The enhanced signal from such hyperpolarized species makes them intriguing MR probes. The file has developed considerably in the past three years, since the applicants invented hyperpolarized-Xe MRI (HypX-MRI) by acquiring MR images of an excised mouse lung that had been inflated with hyperpolarized 129Xe. Improved lung gas space imaging has been demonstrated by others, using the stronger signal from hyperpolarized 3He, but 129Xe is the more interesting nucleus, since its high lipid solubility renders it a promising probe of organs and tissues that have yet resisted MRI techniques. Successful hyperpolarized 129Xe MR spectroscopy and MR imaging of tissues, distal to the lung, crucially depends on whether the T1 of the species in blood is long enough for sufficient magnetization to reach the target tissue. Building on our measurement of a sufficiently long T1 (13.5 sec) in oxygenated blood, to encourage HypX-MRI studies of distal tissues, the applicants proposed to undertake a series of hyperpolarized noble gas magnetic resonance experiments. The aim is to demonstrate the usefulness of the new technique in studying physiological states in animals and humans, and to further its special promise as a clinically important modality. The applicants proposed to develop a high-power, diode laser-driven, optical pumping apparatus to produce sufficient quantities of hyperpolarized 3He and 129Xe to facilitate a variety of biomedical studies. It incorporates a cryogenic storage and delivery system. Pulse sequences of HypX-MRI will be optimized in order to take advantage of the large, non-equilibrium polarization, and to exploit the large chemical shifts observed for 129Xe. RF coils for simultaneous 129Xe and 1H image acquisition will be constructed. Relaxation times (T1 and T2) of 129Xe in blood and tissue samples in vitro will be further studies as a guide to optimizing the imaging pulse sequences. Imaging of ventilated animals will attempt to evaluate usefulness of this technique to studying lung structure and function, and chemical shift imaging techniques will be used to image the brain. The possibility of using HypX-MRI to detect changes in blood flow will be explored, in the hope that it may be a first step towards imaging functional activation of the brain. Finally, experiments will test the feasibility of using this novel methodology to the study of morphology, function, and disease states in human with the goal of developing HypX-MRI for clinical diagnosis.